Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR
Project/Area Number |
16K19461
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Respiratory organ internal medicine
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI MOTOKO 札幌医科大学, 医学部, 教授 (00303941)
TAKAHASHI HIROKI 札幌医科大学, 医学部, 教授 (60231396)
SAKUMA YUJI 札幌医科大学, 医学部, 准教授 (10364514)
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 肺サーファクタント蛋白質D / 変異型EGFR / 肺がん / 糖鎖 / レクチン / 肺サーファクタントタンパク質 / EGFR遺伝子変異 / 肺サーファクタント蛋白質 / EGFR / 肺サーファクタント / 肺コレクチン / SP-D |
Outline of Final Research Achievements |
We have previously demonstrated that SP-D suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. Analysis of patients with lung adenocarcinoma to examine associations between serum SP-D levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, high serum SP-D levels correlated with prolonged overall survival. We herein demonstrate that SP-D downregulates ligand-independent signaling in cells harboring EGFR mutations. SP-D inhibits ligand-independent dimerization of EGFR mutants and dimerization-independent activation of EGFR mutants. SP-D augmented the viability-suppressing effects of EGFR-TKIs. It is possible that the suppressive effects of SP-D on EGF signaling might be implicated in improved clinical outcomes in patients with EGFR mutant lung cancer and high serum SP-D levels.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Surfactant protein A down-regulates epidermal growth factor receptor by mechanisms different from those of surfactant protein D2017
Author(s)
Yoshihiro Hasegawa, Motoko Takahashi, Shigeru Ariki, Atsushi Saito, Yasuaki Uehara, Rina Takamiya, Koji Kuronuma, Hirofumi Chiba, Yuji Sakuma, Hiroki Takahashi, Yoshio Kuroki
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Journal Title
J Bill Chem
Volume: 292
Issue: 45
Pages: 18565-18576
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Surfactant protein A inhibits growth and adherence of uropathogenic Escherichia coli to protect the bladder from infection.2017
Author(s)
Hashimoto J., Takahashi M., Satio A., Murata M., Kurimura Y., Nishitani C., Takamiya R., Uehara Y., Hasegawa Y., Hiyama Y., Sawada N., Takahashi S., Masumori N., Kuroki Y., Ariki S.
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Journal Title
J. Immunol.
Volume: 198
Issue: 7
Pages: 2898-2905
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Surfactant Protein A (SP-A) and SP-A-derived Peptide Attenuate Chemotaxis of Mast Cells Induced by Human β-defensin 3.2017
Author(s)
Uehara Y., Takahashi M., Murata M., Saito A., Takamiya R., Hasegawa Y., Kuronuma K., Chiba H., Hashimoto J., Sawada N., Takahashi H., Kuroki Y., Ariki S.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 485
Issue: 1
Pages: 107-112
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] SP-Dによる変異型EGFR肺がんの制御機構2017
Author(s)
長谷川喜弘, 梅田泰淳, 大塚満雄, 有木茂, 高宮里奈, 齋藤充史, 黒沼幸治, 千葉弘文, 高橋弘毅, 黒木由夫, 高橋素子
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Journal Title
分子呼吸器病
Volume: 21
Pages: 80-83
Related Report
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[Journal Article] SP-A及びSP-A由来ペプチドはヒトβ-ディフェンシン3による肥満細胞の遊走を抑制する2016
Author(s)
有木茂, 上原康昭, 村田雅樹, 高宮里奈, 長谷川喜弘, 齋藤充史, 千葉弘文, 黒沼幸治, 高橋素子, 高橋弘毅, 黒木由夫
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Journal Title
分子呼吸器病
Volume: 20
Pages: 120-123
Related Report
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